Chlamydia species-dependent differences in the growth requirement for lysosomes

Scot P Ouellette; Frank C Dorsey; Simon Moshiach; John L Cleveland; Rey A Carabeo

doi:10.1371/journal.pone.0016783

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Chlamydia species-dependent differences in the growth requirement for lysosomes

Journal article

Open access

Chlamydia species-dependent differences in the growth requirement for lysosomes

Scot P Ouellette, Frank C Dorsey, Simon Moshiach, John L Cleveland and Rey A Carabeo

PloS one, Vol.6(3), pp.e16783-e16783

03/08/2011

DOI: https://doi.org/10.1371/journal.pone.0016783

Handle:

https://hdl.handle.net/2376/116709

PMCID: PMC3050816

PMID: 21408144

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Abstract

Species Specificity

Humans

Cytosol - drug effects

Positive Transcriptional Elongation Factor B - metabolism

Amino Acids - pharmacology

Autophagy - drug effects

Gene Knockdown Techniques

Lysosomes - metabolism

Protein Processing, Post-Translational - drug effects

Cattle

Macrolides - pharmacology

Inclusion Bodies - metabolism

Chlamydia - drug effects

Lysosomes - drug effects

Serum Albumin, Bovine - pharmacology

Inclusion Bodies - ultrastructure

Inclusion Bodies - drug effects

Chlamydia - ultrastructure

Cycloheximide - pharmacology

Chlamydia - growth & development

Lysosomes - ultrastructure

Animals

Models, Biological

Cytosol - metabolism

Mice

Genome reduction is a hallmark of obligate intracellular pathogens such as Chlamydia, where adaptation to intracellular growth has resulted in the elimination of genes encoding biosynthetic enzymes. Accordingly, chlamydiae rely heavily on the host cell for nutrients yet their specific source is unclear. Interestingly, chlamydiae grow within a pathogen-defined vacuole that is in close apposition to lysosomes. Metabolically-labeled uninfected host cell proteins were provided as an exogenous nutrient source to chlamydiae-infected cells, and uptake and subsequent labeling of chlamydiae suggested lysosomal degradation as a source of amino acids for the pathogen. Indeed, Bafilomycin A1 (BafA1), an inhibitor of the vacuolar H(+)/ATPase that blocks lysosomal acidification and functions, impairs the growth of C. trachomatis and C. pneumoniae, and these effects are especially profound in C. pneumoniae. BafA1 induced the marked accumulation of material within the lysosomal lumen, which was due to the inhibition of proteolytic activities, and this response inhibits chlamydiae rather than changes in lysosomal acidification per se, as cathepsin inhibitors also inhibit the growth of chlamydiae. Finally, the addition of cycloheximide, an inhibitor of eukaryotic protein synthesis, compromises the ability of lysosomal inhibitors to block chlamydial growth, suggesting chlamydiae directly access free amino acids in the host cytosol as a preferred source of these nutrients. Thus, chlamydiae co-opt the functions of lysosomes to acquire essential amino acids.

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Title: Chlamydia species-dependent differences in the growth requirement for lysosomes
Creators: Scot P Ouellette - Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College, London, United Kingdom
Frank C Dorsey
Simon Moshiach
John L Cleveland
Rey A Carabeo
Publication Details: PloS one, Vol.6(3), pp.e16783-e16783
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: AI065545 / NIAID NIH HHS G0900213 / Medical Research Council K22 AI052252 / NIAID NIH HHS AI052252 / NIAID NIH HHS R01 AI065545 / NIAID NIH HHS F32 CA123777 / NCI NIH HHS R01 AI065545-05 / NIAID NIH HHS CA123777 / NCI NIH HHS
Identifiers: 99900547780601842
Language: English
Resource Type: Journal article